Exams

Fall 1993
Name:

Recitation day , time ,

7.03 Hour Exam 1

October 1, 1993

Write your name on all five pages.

Indicate your recitationsection on this page

Write all answers on this handout only

Exam begins at 11:05 and ends at 11:55

Time will be announcedwhen 5 and 1 minutes remain,

Problem 1 30 points
Problem 2 30 points
Problem3 40 ooints

Total 100 points

 Name"

1 In the following humanpedigree individuals exhibitinga common inherited allergy to

milk are shown by solid figures and unaffected individuals are shown by open figures.

I
female
O- 1 2

r--] = male
I

III
1 6

IV
1 2 3 4 5 6 7
'7

(a 5pts.) Assumingcompletepenetrance,what isthe probablemode of inheritanceof the

milk allergy?

(b 10pts.) Give the genotypesof the followingindividualsusing + to indicatethe normal

allele and m to indicatethe allelespecifyingthe milkallergy. In ambiguouscases indicateall
possiblegenotypes.

!1-1 111-2

11-2 111-5

11-3

(¢ 15pts.) If cousinsIV-4 and IV-5 havea child together what is the probabilitythat the
childwill have the milkallergy?
 Name:

2 Consider two different antigen molecules produced on the blood cells of wild type
mice according to the biosynthetic pathway below.

enzyme
B_,_,_ antigen I
enzyme /-
A _ intermediate
v enzyme

"_lk antigen2

Mice homozygousfor recessive alleles that block the production of enzyme A (genotype a/a)
do not make either antigen 1 or antigen 2. Mice homozygousfor recessive defects in enzyme
B (genotype b/b) do not make antigen 1. Mice homozygousfor recessive defects in enzyme
C (genotype c/c) do not make antigen 2.

(a 8pts.) Two differenttrue breedingstrainsof mice have been isolated that do not make
either antigen 1 or antigen 2. When an individualfrom one strain is crossedwith an
individualfrom the other strain all of the F1 mice produce both antigens. Write out the
genotypesfor both strains. (Use A, B, and C to designatethe wild type and a, b, and c to
designate the defective alleles of the three enzymes).

(b 12pts.) Two of the F1 mice are crossedto one another. The possible phenotypes for
the F2 progeny are shown below. What proportionof the F2 will be represented by each
phenotype on average?

antigen 1+, antigen 2+ antigen 1+, antigen 2"-

antigen 1-, antigen 2- antigen 1-, antigen 2+

 Name:

(2¢ 10pts.) Among the F2 there will be mice of several different genotypes that are
phenotypically antigen 1- and antigen 2-. Suppose you wanted to test whether a given F2
mouse that does not express either antigen is defective in production of enzyme A. What
genotype would you choose for a mouse used for such a test cross of the F2 mouse?
Describe the possible outcomes of this cross and how you would interpret them.

3 (a 5pts.) Suppose that in an isolated population there exists a very rare inherited
anemia which is autosomal recessive. Given the frequency of the allele for the anemia as q,
calculate the probability that a child will be born with the anemia assuming random mating.
Express your answer as a function of q.

(b 5pts.) What is the probability as a function of q that a given individual in the population
is a heterozygote? Use the approximation that is valid for small q.
 Name:

(¢ 10pts.) In this population marriages between a niece and her biological uncle occur
quite often. Given the niece in such a marriage is heterozygous for the allele for the anemia,
what is the probability that her child will have the anemia? This is the joint probability that her
husband (and uncle) is also heterozygous and that the child of two heterozygotes is
homozygous.

(d 10pts.) Given that uncle-niece marriages occur at a frequency of 0.008, use the
answers derived above to calculate the frequency within the population with which children
with the anemia are produced by uncle-niece marriages. Express your answer as a function
of q.

(e 1Opts.) If half of the children with the anemia come from uncle-niece marriages and half
come from marriages with no obviousinbreeding,what is q? If helpful, you may use the
approximationthat the frequency of random marriagesis about one.
 EXAM #1 SOLUTIONS

a) The mode of inheritance must be autosomal recessive. X-linked recessive is not a

possibility, since male IV,5 is not affected.
b) I1,1:m/+ 111,2:
m/+
11,2:m/m 111,5:
m/m
11,3:m/+ or +/+
c) The probabilitythat the childhas the milkallergyis the joint probabilitythat both parents
are heterozygous multipliedby the probabilitythat the childwill receivetwo copiesof the
mutant gene-one from each parent.
p(mother heterozygous)=2/3 (mother is either +/+ or m/+)
p(father heterozygous)=l
p(childwill inherit both mutant copies)=1/4
total probability= 2/3(1 )(1/4)=1/6

Problem 2:

a) One strain must be of genotype _ while the other must be AAbbc¢. This is the only
way the F1 could produceboth antigens(AaBbCc).
b) antiaen 1+.antigen 2÷ must have the genotype A-B-C-. The proportionwill be
3/4*3/4*3/4 = 27/64 from the crossAaBbCcxAaBbCc.
antiaen 1+.antigen 2- must have the genotype A-B-cc. The proportionwill be
3/4"3/4"1/4 = 9/64

antigen 1-,antigen 2+ must have the genotype A-bbC-. The proportionwill be

3/4"1/4"3/4 = _/64.
antiaen 1-.antioen 2- will comprisethe rest of the population,or 1-(27/64+9/64+9/64)
= 19/64.

c) The possiblegenotypes that would give antigen 1-,antigen 2- phenotypes are:

A-bbcc
aaB-C-
aabbC-
aaB-cc
aabl0cc In order to distinguishthe genotypes that are deficient for
enzyme A, the proper testcross would be to an aaBBCCmouse. Any mouse that isaa will
produceall antigen 1-,antigen Z- offspring when crossedto the above testcross mouse. Any
mouse that has at least one good copy of enzyme A will produceantigen 1+,antigen2+ offspring
Manystudents choseAAbbcc as the genotype for their testcross. This will not allow you to
distinguishthe aabbcc mice from A-bbcc mice. Usingthis testcross, one would concludethe
aabbccmousewasnot deficientin enzymeA, sinceit producesallantigen1-,antigen2-
offspdnglOtherstudentschosea mousethat washeterozygousforA (Aa) fortheir testcross.
Thiswouldnot allowyouto drawa distinctconclusion
betweenaa andAa mice. In theory,if the
mouseto be testedwasaa, 1/2 of the progenyfromthe testcrosswouldbe antigen1-,antigen2-
• If the mouseto be testedwasAa, 1/4 of the progenywouldbe antigen1-, antigen2-. Given
that micedo not havelargelitters,it maybeverydifficultto distinguish
betweenthesetwo
possibilities.Finally,somestudentsoutlineda seriesof crossesfortheiranswer. The
hallmarkof a testcrossisthat it is onlyonecrossthat willallowyouto determinethe genotype
in questionl

Problem

a Random mating means the population is in Hardy-Weinberg equilibrium.

Thus the frequency of children born with the disease is simply o,2.

b With a population in H-W equilibrium the frequency of heterozygotes is

simply 2pq. Since q is small p is about 1, so the frequency of heterozygotes is 2q.

c Since we are told that the niece is a heterozygote we do not use p or q at all
in this part of the problem. If the niece is a heterozygote the chance that the
uncle's sibling has the disease allele is 1/2. If the uncle's sibling is a heterozygote
the chance the uncle has the disease allele is 1/2. If both the uncle and the niece
are heterozygous for the disease allele the chance that they will have an affected
child is 1/4. Thus p(affected child) = (1/2)(1/2)(1/4) = 1/16.

d The chance that any woman is a heterozygote is 2q (see part b). The chance
that this woman marries her uncle is .008. The chance that this uncle/niece
couple have an affected child is 1/16 (seeabove). Thus the frequency within the
population with which children with the anemia are produced by uncle-niece
marriages is: (2q)(.008)(1/16) = o./1000.

e If half the affected children come from uncle-niece marriages and half
come from marriages with no inbreeding we simply set the answer to part d
equal to the answer in part a. q2 = q/lO00. Solving for q we get q = 1/1000.
Name:

Recitation day , time ,

7.03 Hour Exam 2

October 20, 1993

Write your name on all four pages.

Indicate your recitation section on this page

Write all answers on this handout only

Exam begins at 11:05 and ends at 11:55

Time will be announced when 5 and 1 minutes remain.

Problem 1 30 points
Problem 2 40 points
Problem3 30 ooints

Total 100 points

 Name:

1 The two hypothetical autosomal human genes xey and stm are 10 map units
apart. Dominant alleles of xye are completely penetrant and cause crossed eyes.
Dominant alleles of stm are completely penetrant and cause small thumbs. A cross-
eyed, small thumbed woman marries a normal man and they have four children. Two
of the children are cross-eyed and two of the children have small thumbs.

(a 10 pts) Would you expect either of the woman's parents to be cross-eyed and
have small thumbs?

(b 10 pts) The woman is pregnant with a fifth child. What is the probability that this
child will be cross-eyed and have small thumbs? (Hint m don't use Bayes Theorem for
this problem.)

(¢ 10 pts) Oocytes, are the diploid cells that by meiosis, give rise to the gamete egg
cells in a woman. What fraction of the oocytes in the woman in this question, will have
a crossover event occur between the xey and stm genes during meiosis?
 Name"

2 Consider two different yeast genes that we will call RED1 and RED2.
Recessive mutations in either gene cause the yeast colonies to turn red rather than the
normal white color. A haploid red1" mutant is crossed to a haploid red2- mutant.
The resulting white diploid is sporulated and tetrads are dissected. There are three
types of tetrads with respect to colony color:

_T..v.D.9_[ Type II TvDelII

2 red: 2 white 3 red" 1 white 4 red

(a 5 pts) Classify each of the types as either PD, NPD or T tetrads.

TypeI= TypeI1= TypeIII=

(b 10 pts) Of 100 tetrads dissected 6 are of type I, 34 are of type II, and 60 are of
type II1. What is the measured genetic map distance between RED1 and RED2?

(¢ 10 pts) The TRP1 gene is completely linked to its centromere. When a trpl"
mutant is crossed to a red1" mutant and 100 tetrads are dissected, no T type tetrads
are found. How many T type tetrads would you expect to find if a trpl" mutant is
crossed to a red2" mutant and 100 tetrads are dissected?

(d 15 pts) A mutation in a new red gene, RED3, is discovered. When a red1"

mutant is crossed to a red3" mutant, tetrads of the three types described above are
seen. For this cross, of 100 tetrads dissected 15 are of type I, 67 are of type I1,and 18
are of type III. If a red3" mutant were crossed to a trpl" mutant, how many tetrads out
of 100 would you expect to have 2 red, Trp + spores and 2 white, Trp- spores?
 Name:

3 Consider a phage for which there are two temperature sensitive mutations, tsl-
and ts2". Phage with either of these mutations will form plaques at 30° but not at 40"
(you should assume that the double mutant tsl", ts2" will also form plaques at 30" but
not at 40°). To perform a recombination test between these mutations tsl", ts2 + and
tsl +, ts2" phage are infected into host bacteria so that each bacterial cell gets
multiple copies of both phage. The infected cells are grown at 30° to allow growth of
the mutant phage and to allow recombination between phage.

(a 10 pts) Given that the distance between tsl and ts2 is 8 m.u., what fraction of
the phage from this cross will be wild type? In other words, what fraction of the phage
will make plaques when plated at 40°?

(b 10 pts) A new mutation that causes mottled plaques is isolated. The allele that
causes the mottled phenotype is designated mot" whereas the wild type allele is
designated mot +. A tsl", mot" phage is crossed to a wild type (tsl+, mot +) phage.
The phage resulting from this cross are plated at 40" and 4% make mottled plaques.
What is the distance between tsl and mot in map units?

(¢ 10 pts.) A tsl", ts2 +, mot + phage is crossed to a tsl+, ts2", mot" phage. From
this cross, phage that can grow at 40" are isolated and it is found that 96% of these
phage have mottled plaques. On the map below show the position of the mot locus.
Be sure to indicate the distance to either tsl or ts2 in map units.

ts 1 ts2

I 8m.u.
 Answers to 7.03 Exam #2

1 a) No. You would expect that most offspring come from non-recombinant gametes. Since the
children are small thumbed, normal eyed or normal thumbed, cross eyed these are most likely the
non-recombinant genotypes. Therefore the mother's genotype is xye +/+ smt, so one grandparent
was only cross eyed and the other only small thumbed.

1 b) 5%. From the definition of map units we know there is a 10% chance of being a recombinant
gamete for xye and stm. Remeber that half of those recombinants will be wt and half will be stm
and xye. So there is only a 5% chance the child will be double mutant.

I c) 20%. From the definition of map units we know that 10% of the gametes are recombinant.
There must be crossovers in 20% of the oocytes to yield 10% recombinant gametes.

20/100 oocytes with a cross over --> 40/400 recombinant chromosomes-->

-->10% recombinant gametes.

2 a) Type I = NPD Type 2 = TT Type 3 = PD

2 b) 35 m.u. Just apply the tetrad formula for linked genes.

35 m.u. = 100134 + 6(6)/2(100)]

2 c) 34 TT expected. The fact that the trpl- and red1- cross yielded no tetratypes means that the
two genes are unlinked, and both are completely linked to their respective centromeres. For the
trpl-, red2- cross we know the markers are unlinked (because red1 is linked to red 2 and red1 and
trpl are unlinked). Any crossover event that gives a tetratype tetrad for markers red1 and red2
(the situation in problem 2b) will lead to a tetratype tetrad between markers red2 and t-rpl. So the
answer is you'd expect the same number of tetratypes as in 2b, 34 tetratypes.

2 d) expect 17 or 16.6. The data in the problem suggests the two marker s are unlinked. So you
expect a 1:4:1 ratio of PD:TT:NPD. Thus 1/6 of the tetrads should be of PD (2 red, trp+ 2 white
trp-). 1/6(100)=16.6 or 17.

3 a) 4%. 8 m.u.= 100(# recombinant phage)/total

The number of recombinant phage is 8%. Remember only half of the recombinants are wt the
other half are tsl-,ts2-. So the fraction of wt will be .08(1/2)=.04

3b) 4 m.u. Of the phage growing at 40°C (tsl+) 4% of them are recombinant (mot-). mu = #
recombinant phage out of the total. We are missing half the recombinant phage because they are
tsl-,mot+ and can not grow at 40°C. However we are also missing half the total because one of the
parentals tsl-,mot- also can not grow at 40°C. So map units is simply .04(100).

3c )
The rare class is tsl+, ts2+, mot+, they represent only 4% of the plaques growing on the plate. This
must be the result of a double crossover event. Therefore tsl is between mot and ts2.
Name:

Recitationday ., time , TA

7.03 Hour Exam 3

November 10, 1993

Write your name on all six pages.

Indicate your recitationsection on this page.

Do all work on this handout only.

Exam begins at 11:05 and ends at 11:55.

Time will be announcedwhen 5 and 1 minutes remain.

Problem 1 35 points
Problem 2 35 points
problem3 30 ooints

Total 100 points

 Name:

1 Some mutations of the Lac operon are defined as follows:

IS : An allele of the repressorthat is unable to bind inducer molecule but will still
bind to operator DNA.

I-d : A dominant repressor mutationthat does not bindthe operator and prevents
wild-type repressorfrom binding operator.

O¢ : An operator mutationthat will not bind repressor.

P" : A promoter mutationthat will not bind RNA polymerase.

Z" : An allele of the lacZ gene that does not make active B-galactosidase enzyme.

Y" : An allele of the lac permease gene that does not make active permease.

The levels of B-galactosidaseactivity in a wild type strain with or without inducer are
shown below

.IPTG -.IP_.T.D

I+ p+ O+ Z+ high low

Fill in this table indicatingeither high or low levels of r:_-galactosidasefor each of the
following strains with or without inducer.

.IPTG -_LE.T.D

(a 5pts) Is P+ O¢ Z'/F'I + P+ O+ Z+

(b 5pts) IS p+ O+ Z'/F'I + P+ O¢ Z+

(c 5pts) I+ P+ O+ Z'/F'I + P" O¢ Z+

2
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Starting with a strain that is I+ P+ O+ Z'Y+/F'I÷ P+ O÷ Z+Y - you isolate two

differentmutants that _ express 8-galactosidaseactivity, For each mutant
you assay both 8-galactosidase activity and permease activity with or without inducer.

I_-galactosidase activiW

+IPTG -IPTG

Mutant 1 high high

Mutant 2 high high

Permease activity

+IPTG -IPTG

Mutant 1 high low

Mutant 2 high high

Assumingthat each mutantalters only one element of the la¢ operon, figure out the
genotypes of Mutant 1 and Mutant 2. If morethan one genotype is possible give all of
the possibilities. You need only considerthe types of mutant alleles given at the
begining of this problem. Undesignatedelements in your written genotypes will be
assumed to be wild type.

(d 10pts) Mutant 1 = IF'

(e 10pts) Mutant 2 = /F'

 Name

You have two true-breeding varieties of elongated pumpkins

(strain#1 and strain#2). Wild-type pumpkins are round. When crossed to
wild type, strain#1 and strain#2 produce round pumpkins.

(a l Opts) You cross strain#1 with strain#2 and find that all F1 pumpkins
are elongated, and after self-fertilization you find that all F2 pumpkins
are elongated.

i. What are the genotypes and phenotypesof the parents, the F1 and F2
generation.

i i. Is the phenotype of strain#1 and strain#2 dominant or recessive to

the phenotype of the wild-type strain?

iii. Circle the concept(s) that characterize(s) the observed relationship

between strain#1 and strain#2 best:

complementation epistasis redundancy

suppression enhancement

4
 Name:

(b 25pts) You discover a new true-breeding variety of round pumpkin

(strain#3) and make the following observations:
-When strain#3 is crossed to wild type, the F1 progeny pumpkins are
round, and after self-fertilization, 3/16 of the F2 pumpkins are elongated
and all other pumpkins are round.
-When strain#3 is crossed to strain#I, the F1 pumpkins are elongated,
and after self-fertilization, 1/4 of the F2 pumpkins are round and 3/4 are
elongated.

i. Give the genotypes and phenotypes of the parents, the F1 and F2

generation of the cross between strain#3 and wild type.

ii. Give the genotypes and phenotypesof the parents, the F1 and F2
generation of the cross between strain#3 and strain#1.

i ii. Is the phenotype of strain#3 dominant or recessive to that of

strain#1 ?

iv. Circle the concept(s) that characterize(s) the observed relationship

between strain#1 and strain#3 best:

complementation epistasis redundancy

suppression enhancement

5
 Name:

3 Consider three genes in E. co//A, B, and C whose order and exact spacing are
not known. Transducing phage P1 is grown on an A + B+ C÷ host and this phage
lysate is used to infect an A" B" C" recipient. A + transductants are selected and the
frequencies of cotransduction of the other markers are shown below:

A+ B+ C+ 80%
A+ B+ C" 4%
A+ B" C+ 15%
A+ B" C" 0.6%

(a 1Opts) Of the genetic intervals A-B and A-C which is larger?.

Give cotransductionfrequenciesfor B and C.

(b 15pts) An F' factor that carries the wild-type copiesof all three genes A +, B+,
and C + is mated into an F" A" B" C" recipient. From this strain an Hfr is isolated that
transfers A+ and B ÷ early and C+ very late. Draw the structure of the F' (not the Hfr)
showingthe order of the A, B, and C genes and the orientationof the odgin of transfer.

(¢ 5pts) In cloning of the A gene a new gene D is discovered 10 kilobases away.

The transducing phage P1 packages random 50 kilobase segments of the
chromosomal DNA per phage. Which frequency is greater: The frequency that A and
D are packaged into the same phage or the cotransductionfrequency of A and D
under A+ selection? Explain briefly.

6
 Solutions to Exam 3 mean : 64

Problem 1

a) Since the super repressor (IS), a trans-acting factor, is present there will be no !
lacZ expressed under any conditions. O c has no effect since it is cis-acting (on Z-). Thus
the answeris 1ow low

b) Now Oc is in cis with Z+ so this gene is expressed constitutively: h i g h high

c) Since there is no promoter (P-), a cis acting element, to drive any transcription.
Thus no lacZ is expressed under any conditions: low low

d) The only way to express Z constitutively and have Y under normal regulation is to
alter a cis-acting element: I*P÷O÷Z'Y÷/F ' I*P*OeZ÷Y"

e) The only way to have constitutive expression of both Z and Y with only one
change is to have I-d present. It can be on either the chromosome or the F' since I is
trans-acting: I'dP÷O*Z'Y÷/F ' I÷P÷O+Z÷Y" o r I÷P÷O÷Z'Y÷/F' I-dp÷o÷z*Y"

A few students changed the same element on both the F' and the chromosome. This
would work if they both had 0 c or I_. Getting two mutations at once is very unlikely.

Problem 2a)
i (6pts) The cross of each elongated mutant to the round wild-type yields all round
pumpkins. This tells you that both strains carry recessive mutations. When these two
strains are crossed to each other the F1 are all elongated. Since both mutations are
recessive and the F1 has the mutant phenotype these two mutations must be in the same
gene!!! This is in fact a complementation test. The two mutations fail to complement
each other and thus are in the same gene. Note that there is only one gene involved
here. Always go for the simplest model that fits all the data because we really are not
trying to trick you!

Pumpkin Genotype Phen ot y pe

Wild type AA round

Strain 1 alal elongated

Strain 2 a2a2 elongated

F1 (lx2) ala2 elongated

F2 ala2, alal, a2a2 elongated

ii (2pts) Both strains are recessive to wild-type. (See above)

i

iii (2pts) Complementation (See above)

Problem 2b)
i.(10 pts.) The fact that 3/16 of the progeny in the F2 generation are elongated
tells us that there are two mutant genes segregating independently. Therefore, strain 3
must contain two mutations in two genes. Since it is a true-breeding strain, it must be
homozygous for these two mutations. If we designate the two genes as A and B, then the
parental, FI, and F2 crosses are as follows:

Pompkin Genotype Phenotype

wild type AABB r ou n d
strain 3 a a b b ro u n d

F1 (3xWT) AaBb round

F2 9 A_B_ round
3 aaB_ elongated
3 A_bb round
1 aabb r o u nd

Therefore, strain 3 contains a mutation (designated as "a") that causes elongated

pumpkins. However, strain 3 also contains a mutation that either suppresses, or is
epistatic to, the "a" mutation and causes round pumpkins. This mutation (designated as
"b") only suppresses, or is epistatic, when it is homozygous. That is the reason we see
3/16 of the progeny in the F2 are elongated, since they are homozygous for aa, but are
not homozygous for bb.
ii. (10 pts) Since in the F2 generation we see a 3:1 ratio, there must be only one
gene segregating that is different between strain 3 and strain 1. We know from above
that strain 3 carries a mutation that causes elongated pumkins. We also know that strain
1 carries a mutation for elongated pumpkins, but does not carry a suppressor or epistatic
mutation. Therefore, we can conclude that strain 3 and strain 1 carry mutations in the
same gene which contribute to the elongated pumpkin phenotype. They differ in the
suppressor, or epistatic gene:

Pumpkin Gen0typ_ Phenotype

strain 1 aaBB elongated
strain 3 a a b b round

F1 (lx3) aaBb elongated

F2 1 aaBB elongated
2 aaBb elongated
1 aabb r o und

Some students tried to explain the 3:1 ratio as actually a 12:4 ratio resulting from a
dominant mutation. This model is inconsistent with the fact that strain 1, when crossed
to wild type, gives all round pumpkins. Therefore, the mutation in strain I must be
recessive (see part a,ii.).

iii. (3pts.) When strain 3 is crossed to strain 1 all the resulting progeny are
elongated. The phenotype of strain 3 is therefor recessive to that of strain 1.

iv. (2pts.) As stated above, the results show that strain 3 contains a mutation that
suppresses, or is epistatie to, the mutation that causes elongated pumpkins. In
addition, these results tell us that strain 1 and strain 3 carry mutations in the same gene.
Therefore, the mutations do not complement each other. Credit was given for any of
the correct answers, but no credit was given if an incorrect answer was circled.
 Problem 3:

a) Cotransduction frequencies for A-B: 80% +4% = 84 %

Cotransduction frequencies for A-C: 80% + 15% = 9 5 %

The closer two markers are to each other the higher the co-transduction
frequency. Thus the A-B interval is the larger of the two.

b) Many students misread this question. The question did not ask for the F'
derived from the Hfr strain. It asked for the F' that integrated to b¢c0m¢ an Hfr strain.
The order of the genes was determined from the information in part a).
The map derived from the data in part a was as follows:

_+ A+ ¢+ C+ A+ B+
x1 x2 or x2 x1
_- A- ¢- ¢- A- t_-
A crossover outside both B and C A+B+C+ 80%
A crossover outside B and in interval 2 A+B+C- 4%
A crossover outside C and in interval 1 A+B-C+ 15%
A crossover in interval 1 and interval 2 A+B-C- 0.6%

Note that other combinations are not possible since they result in A- (we selected A+).

The crossover event to generate an Hfr that transfers A+ and B+ early and C+ late:

Ft

\ B+ A-t- 17+ J
1
c
_ C+ A+ !_+ _t/

_- A- I C- chrom. ¢- _ A- B-

B- A-¢+ _ l_+ A+ ¢- C- A+ B+ IlL ¢+ A- B-

c) Two answers were accepted:

The frequency that A and D are both packaged into the same phage, given that A
is packaged, is greater than the co-transduction frequency of these two markers since
this requires both co-packaging and an appropriate recombination event.

The frequency that A and D are packaged into the same phage is actually quite low
if you do not assume that a phage has either marker. Since you select for A+
transductants you might expect that since D is only 10kb away it will be co-transduced at
a reasonable frequency. With this explanation it is possible to imagine that the co-
transduction frequency of A and D might be greater than the frequency with which
they are packaged into the same phage.
No points were awarded if there was no explanation to justify the answer.
 NalTle

T.A.

7.03 FINAL EXAM

December 14, 1993

WRITE YOUR NAME ON ALL 14 PAGES.

INDICATE YOUR RECITATION SECTION ON THIS PAGE.
WRITE ALL ANSWERS ON THIS HANDOUT ONLY.

The exam begins at l:30pm and ends at 4:30pm.

Time will be announced when 15 minutes and 3 minutes remain.

Advice: if you get stuck on one question, go on to the next one!

Three pages of scratch paper are at the end.

Problem 1 30 points
Problem 2 25 points
Problem 3 20 points
Problem4 15 points
Problem5 12 points
Problem6 12 points
Problem7 12 points
Problem8 34 points
Problem 9 40 points

Total 200 points

 NalTle

1 Consider an autosomal allele in rabbits that causes extreme nearsightedness when

homozygous and that causes partial nearsightedness when heterozygous. Two
populations of rabbits are tested for nearsightedness and the frequencies within these
populations of rabbits with vision problems are given below.
Extremely nearsighted Partially nearsighted
Population
A 0.18 0.24
Population
B 0.09 0.42

(a 5pts) Is population A in Hardy-Weinberg equilibrium? Yes ('No-')

Circle the correct answer.

Is population B in Hardy-Weinberg equilibrium? Y(_) No

Circle the correct answer.

(b 5pts) Rabbits from the two populations are mixed in equal numbers. After one
generation of random mating within this new population what will the frequencies of
extremely nearsighted and partially nearsighted rabbits be?

_._ : 2_
0.3_0,{ - 0.%

Extremely nearsighted Partially nearsighted

2
 Naine

Question 1 continued

A population of rabbits is in Hardy-Weinberg equilibrium for the nearsightedness allele

until a road is built through their territory putting the nearsighted rabbits in grave danger.
We will consider two possible modes of selection now imposed on the rabbit population.

Mode 1: Extremely nearsighted rabbits are always killed by cars before they
reproduce. Partially nearsighted and normal rabbits are essentially never hit by cars.

Mode 2: Both extremely nearsighted and partially nearsighted rabbits have a 20%
chance of being killed by a car before they reproduce. Rabbits with normal eyesight are
essentially never hit by cars.

(c 10pts) If the frequency of the nearsightedness allele is 0.1, which mode of

selection will drive down the allele frequency faster in the first few generations after the
road is built?

f_10</-¢{ ": {o_ : S_7- _vr s:l -_'2 O.oi

_:.i

(d lopts) If the frequency of the nearsightedness allele is 0.5, which mode of

selection will drive down the allele frequency faster in the first few generations after the
road is built?

nT_>
de 2_ io_s = "_Z_ + _ " D"-s

3
 Name

2 Consider two temperature sensitive mutations in yeast, tsml and tsm2. When a
tsml strain is crossed to a tsrn2 strain the diploids are not temperature sensitive. When
these diploids are sporulated, tetrads of three types are found. In the table below ts-
means temperature sensitive and ts+ means wild type growth.

TypeI T_vpeII T_vpe III

ts+ ts+ ts-
tS+ ts- tS"
tS" tS" ts-
tS" tS" ts"

N ::) --r
(a 7pts) From 50 tetrads; 2 are type I, 12 are type II and 36 are type III. What is
the distance in map units between tsml and tsm2?

(b 8pts) If the strains from this cross were not ordered into tetrads, the map
distance between the two mutations could still be calculated. Using the standard
def'mition of map units and the fraction of the 200 strains from the cross that are ts +,
calculate the distance between tsml and tsm2.

z/. so
(c 5pts) Say you need a strain that has both tsml and tsm2 mutations. Without
any further testing, which of the strains from the tetrad analysis would you pick?

(d 5pts) Four strains from one of the type IItetrads

have the following properties:

Strain 1: Mating type ct, ts+

Strain 2: Mating type (x,ts-
Strain 3: Mating type a, ts"
Strain 4: Mating type a, ts"

Strain 2 is crossed to strain 3 and the resulting diploid is ts+. Which of these four strains
has both the tsml and tsm2 mutations?

4
 Nafne

3 (a 10pts) The proC gene lies very close to the lac operon on the E. coli
chromosome, proC shows 90% cotransducfion with a lad" nonsense mutation and 80%
cotransduction with a laeZ" nonsense mutation. In a transduction experiment, phage are
grown on a proC +, laeI', lacZ" host. The resulting transducing phage are used to infect a
proC', lad +, laeZ + recipient and proC + transductants are selected. Three phenotypic
classes are found among the proC + transductants: regulated expression of [5-
galactosidase, constitutive expression of [5-galactosidase, and no [5-galactosidase
expression. Give below the expected frequencies of each of the three phenotypic classes
(assume no quadruple crossovers).

Reg01ated expression Constitutive

__expressi°n NO expression

."_ , _._oC
_ q, _ _- 3 / _-__ _

(b 10pts) The proB gene is also closely linked to the la¢ operon. In a transduction
experiment, phage are grown on a proB +, lacI', laeZ" host and are used to infect a
proB', lad +, lacZ + recipient. Of the proB + transductants, most show either regulated
expression or no expression of _galactosidase. Transductants that show constitutive [5-
galactosidase expression are extremely rare. Draw a map of the lac region showing the
relative order of the proC, proB, lad and lacZ genes (don't worry about distances).
,_

5
 Name

4 Below is the pedigree of a family in which a rare, fully penetrant neurological

disorder is inherited. A particular DNA probe is used to analyze a restriction enzyme
fragment digest from each of the members of the family. Restriction fragments from
each individual are found to hybridize with the probe as shown below.
(circle female, square male, f'dled afflicted.)

Generation

, '@
,, 4KI
III 11

'.... :.... 5kb

!

---- -,-- -,"- 2kb

I
!

I1-1 11-2 I-1 I-2 il-3 II1-1 111-2 111-3111-4 11-4

(a 2pts) What is the mode of inheritance of this disorder?

(b 3pts) What is the size of the DNA fragment that is linked to the mutation
responsible for the disorder?

(c 5pts) Identify all unaffected members of the family who probably are carriers..
i-9_
7_-3
_L-(
(d 5pts) Could any other unaffected member(s) have inherited the mutation?
Explain briefly!

6
6 (12pts) You have two true breeding brown-eyed stocks of Drosophila. When
individuals from either stock are crossed with red-eyed wild-type flies you have a 3: I
ratio of brown to red-eyed phenotypes in the F2 generation. When individual flies of the
two brown-eyed stocks are crossed with each other, all of the F1 flies are brown-eyed.

For each question below, circle the T preceding each statement that is true and the F
preceding each statement that is false. More than one statement may be true.

T_ F 1. The mode of inheritance is most likely recessive.

F 2. The mode of inheritance is most likely autosomal.
T (_) 3. The mode of inheritance could include two genes.
F 4. The F2 progeny from the cross between the brown-eyed stocks could be
all brown- eyed.
T (_) 5. The F2 progeny from the cross between the brown-eyed stocks could
display a 1:1 ratio of brown eyed to wild-type phenotypes.
T @ 6. The F2 progeny from the cross between the brown-eyed stocks could
display a 15:1 ratio of phenotypes.

7
 NaiI2e

8 You have a strain of Drosophila homozygous for an autosomal recessive mutation

(purple (pr)) that causes a recessive brown eye color. In your pr strain you f'md a male
fly which has the wild-type eye color red. You assume that this is a suppressor mutation
which you call sup-1. You cross the red-eyed, sup-1 male with females from the pr strain
and f'mdthat all female progeny are red-eyed and all male progeny have brown eyes.

(a 3pts) Is the suppression caused by the sup-1 mutation recessive or__

(b 3pts) Is sup-1 autosomal o@

(c 8pts) Determine the phenotypic ratio of brown and red-eyed females and males
in the next (F2) generation. (Be sure to specify ratios among males and females!)

brown red
females 1 I
males t ]

You are given a second red eyed stock that is homozygous for pr. Assuming that this is a
new suppressor mutation, you call this mutation sup-2. You cross females from this
strain to the sup1 red-eyed male from (a). In the F1 progeny all females have red eyes
and all males have brown eyes.

(d 8pts) Determine the phenotypic ratio of brown- and red-eyed females and males
in the next generation (F2).

brown red
females 3 -_
males 3 5